JP3067208B2 - Quadrupole mass spectrometry using applied signal with non-resonant frequency - Google Patents

Abstract

A mass spectrometry method in which a combined field (comprising a trapping field and supplemental field) is established and at least one parameter of the combined field is changed to excite ions trapped in the combined field sequentially (such as for detection). The supplemental field is a periodically varying field having an off-resonance frequency, in the sense that the supplemental field frequency nearly matches (but differs from) a frequency of motion of an ion stably trapped by the trapping field alone. Sequential ion excitation in accordance with the invention can rapidly excite each ion to a degree sufficient for a desired purpose but insufficient for ejection from the trap. The amplitude of the supplemental field is kept sufficiently high to excite ions (via an off-resonance excitation mechanism) before they undergo resonant excitation.

Description

DETAILED DESCRIPTION OF THE INVENTION CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is related to U.S. patent application Ser.
No. 034,170 is a continuation-in-part application, which is issued on May 14, 1992.
No. 07 / 884,455, filed on Feb. 28, 1991, is a continuation application of US Patent Application No. 07 / 662,191 filed on Feb. 28, 1991. These earlier applications are incorporated herein by reference.

FIELD OF THE INVENTION The present invention relates to mass spectrometry methods, in which ions are stably captured in an ion trap and then selectively excited for detection. More specifically, the present invention stably captures ions by a trapping field, and designates a supplementary field having a frequency substantially coincident with (but different from) the frequency component of the frequency band of the oscillation of the selected trapped ion as the trapping field. This is a method in which a binding field is formed by superimposing, and the binding field is changed to sequentially excite selected and stably captured ions.

BACKGROUND OF THE INVENTION In one type of conventional mass spectrometry, a binding field (consisting of capture and supplementary field elements of different spatial geometries) is established in an ion trap and the binding field is altered to stably detect it. The captured ions are excited resonantly. For example, U.S. Pat. No. 3,065,640 (patented Nov. 27, 1962) discloses a three-dimensional quadrupole ion trap in connection with FIG. It is DC voltage 2
Vdc and AC voltage 2Vac are applied across the end electrode 13 and the ring electrode 11 of the trap to form a quadrupole trapping field in the trap, the supplementary voltage (DC component Vg and AC component
2V _β ) to the end electrode 12 of the quadrupole trap and
The point applied across 13 to form a coupling (capture and replenishment) field in the trap, and the voltage Vg applied simultaneously
Altering the coupling field by increasing one or both of Vdc and Vdc to teach points to eject trapped ions from the trap via hole 25 through end electrode 12 for detection by an external detector 26 (e.g., , Column 3, lines 13-18, and column 9, lines 9-23).

In one type of conventional mass spectrometry technique, known as the "MS / MS" method, ions having a mass-to-charge ratio (hereinafter referred to as "m / zn") within a selected range (referred to as the "parent ion"). Is isolated in an ion trap. Thereafter, the stably captured parent ion (for example,
The ions are separated or directed to separate (by bombardment with background gas molecules in the trap) to produce ions known as "daughter ions", which are then ejected from the trap (typically Is detected by resonance ejection).

For example, US Pat. No. 4,734, issued on Apr. 5, 1988
No. 6,101 describes a three-dimensional quadrupole trapping field (established by applying a trapping voltage to the ring and end electrodes of a quadrupole ion trap) where ions (with m / z within a given range) are applied.
Disclosed are MS / MS methods captured within. The trapping field is then scanned to continuously eject unwanted parent ions (non-parent ions having the desired m / z) from the trap. The capture field is then changed again so that daughter ions of interest can accumulate. The captured parent ions are separated to produce daughter ions, which are continuously (in order based on mass-to-charge ratio) ejected from the trap for detection.

U.S. Pat. No. 4,736,101 establishes (in column 5, lines 16-42) a supplemental AC field in the trap after the separation period (in addition to the capture field), during which the scanning voltage is scanned (or during that time). Keeping the capture voltage constant and supplementing AC
(Travel the frequency of the field). The frequency of the supplemental AC field matches one of the components of the frequency band of the trapped ion oscillation, so that the supplemental AC field has a permanent (secular) frequency for each trapped ion (in a changing coupling field). When the frequency coincides with the frequency, the trapped ion train is ejected from the trap in a resonant manner.

Similarly, U.S. Pat. No. 4,882,484, issued Nov. 21, 1989, teaches the resonant ejection of stably trapped ions from a three-dimensional quadrupole (near quadrupole) trap, which Replenishing by scanning the established binding field (with RF capture and replenishment AC field components) in the ion trapping area, for example by scanning the replenishment field frequency or while scanning the capture field parameters This is achieved by keeping the frequency of the field constant.

The problem with conventional resonance excitation techniques (including the resonance ejection method) is that changing the parameters of the binding field is carefully controlled during resonance excitation to simultaneously eject different ion species (loss of mass spectrometry).
And other undesirable interference effects must be avoided. For example, conventional resonance excitation methods must be considered, such as keeping other coupling field parameters constant while sweeping or scanning the supplemental AC field components of the coupling field.
In this case, the peak-to-peak amplitude of the AC replenishment voltage signal that establishes the replenishment AC field component must be carefully controlled (it must be maintained at a particular amplitude to establish the resonance of the ions of interest. In addition, the rate of change of the AC frequency of the refill voltage signal must be carefully controlled to avoid unacceptable loss of mass resolution due to simultaneous ejection of different ion species.

Quadrupole mass spectrometry and its applications, published in 1976 by Elsevier and edited by PHDawson (Quadrupo
le Mass Spectrometry and its Applications)
From page 50 to page 50, the frequency of the supplementary field utilized during resonance excitation approximates, but differs from, the resonance frequency of stably trapped ions, causing ions having different resonance frequencies to undergo varying coupling. Disclosed is that the field can be excited simultaneously for detection. This is said to undesirably limit the resolution.

Another prior art technique for exciting stably trapped ions is known as "mass selective unstable state" excitation. Examples of this technique are disclosed in the above-cited U.S. Pat. No. 4,882,484 and European Patent Application Publication No. 350,159A (published Jan. 10, 1990).

In mass selective labile excitation, a trapping field (typically a quadrupole trapping field) is established in the trapping region to stably trap ions and to sweep one or more parameters of the trapping field. (Or scanning) so that the captured ions are continuously unstable. Each stably trapped ion is characterized by parameters located at locations within the stability determined by the trapping field. FIG. 2 is an example of a stability diagram for a quadrupole capture field (FIG. 2 is described in more detail below). Referring to FIG. 2, "a" and "q" in the stability envelope (in the area bounded by the four curves labeled βr = 0, βz = 1, βr = 1, and βz = 0). Can be stably trapped in the quadrupole trapping field (parameters “e” and “m” in FIG. 2 indicate charge number and mass, respectively). In performing mass selective labile excitation, the changing trapping field destabilizes the ions, and the "a" and / or
Alternatively, by moving the parameter “q” to the outside of the stability diagram (from within the stability diagram), those ions are ejected.

In some conventional mass selective unstable excitation methods, a fill field is established in the trap during the sweep or scan of the capture field (AC oscillator connected to one or both electrodes). For example, the above-mentioned European Patent Application 350,159A (3rd
(From column line 58 to column 4, line 25), the point at which a supplemental AC voltage is applied to the end electrodes of the quadrupole ion trap while sweeping or scanning the parameters of the quadrupole capture field in the quadrupole ion trap. Teach. The application also teaches that the parameters of the quadrupole capture field can be fixed and the supplemental AC frequency can be swept or scanned to complete the mass selective unstable ejection. The application further states that the quadrupole capture field is RF
It has a frequency component, the frequency of the supplemental AC voltage is approximately equal to half its RF frequency (eg, within plus or minus 20 percent of half the RF frequency), and the supplemental AC voltage has ion motion in the z (axis) direction. The point which has the frequency which coincides with the characteristic frequency of is taught.

In another conventional method of trapped ion excitation disclosed in U.S. Pat. No. 4,749,860 issued June 1988, a supplemental AC voltage sweeps or scans the quadrupole trap field parameters in a quadrupole ion trap. (E.g., during period C in the scan shown in FIG. 2 of U.S. Pat. No. 4,749,860) applied to the end electrode of the quadrupole ion trap. The frequency of the replenishment AC voltage is selected to resonately eject a series of stably trapped ions. At the same time, other trapped ions are said to be continuously unstable in the changing binding field.

However, the disadvantage of mass-selective unstable excitation is that the dynamic range for the analyzed mass is very limited with the number of ions that can be accumulated and sufficient mass spectrometry. When the method according to the present invention is implemented, its disadvantages can be avoided by extending the dynamic range, and the above-mentioned disadvantages of the conventional resonance excitation method can also be avoided.

In connection with quadrupole mass filter operation rather than three-dimensional quadrupole capture operation, the above-mentioned "Quadrupole Mass Spectrometry and Its Applications" (1976) describes the use of a sinusoidal supplementary field on pages 74-76. Overlapping the field establishing a pole mass filter teaches that the frequency of the supplementary field differs by a small amount (Δω) from the permanent frequency of selected ions propagating through the filter. Such a refill field (which can be referred to as an "approximately resonant" or "non-resonant"("off-resonance") refill field is such that motion through the filter is such a permanent It is said that ions with a target frequency can be separated (filtered) (by establishing beat frequency conditions) from ions with a permanent frequency whose motion is slightly different. However, that document applies a "non-resonant" field as one component of a changing binding field (established in a three-dimensional ion trap) to continuously excite (resonantly) selected trapped ions. It does not suggest that it must be (by a mechanism different from excitation or mass selective unstable excitation). Also, in connection with mass filter operation, not three-dimensional trap operation,
U.S. Pat. No. 2,950,389, issued in 1960, discloses that the application of an approximate resonant fill field separates ions whose motion through the filter has a first permanent frequency from ions whose motion has a slightly different permanent frequency (filter). Teach what you can do.

SUMMARY OF THE INVENTION The present invention is a method for mass spectrometry, comprising the steps of establishing a binding field (comprising a capture field and a supplementary field), and altering at least one parameter of the binding field to reduce ions trapped in the binding field. Exciting sequentially (eg, for detection). The refill site has a frequency of the refill site,
It is a periodically changing field having a "non-resonant" frequency in the sense that it approximately matches (but differs) the frequency of the frequency component of the oscillation frequency band of the ions stably captured only by the capture field. Here, the refill field may be referred to as a "non-resonant" field.

Continuous ion excitation (sometimes referred to herein as "non-resonant" scanning or excitation) according to the present invention can cause an instantaneous ejection of an ion train from the trap (or detect each ion in the train). Can be instantaneously excited to a sufficient degree for the desired purpose, such as the trajector of each ion within the continuum.
y) because the refill field increases each ion mass trajectory to a desired amount within a desired short period of time with sufficient magnitude peak-to-peak amplitude, This is done without establishing a state or before a resonance state is established between the ionic frequency of the motion and the fill field frequency.

In one type of embodiment, the trapped ions are excited continuously by keeping the non-resonant field constant while changing at least one parameter of the trap field component of the binding field. In another embodiment, the capture field is excited continuously by changing (eg, sweeping or scanning) at least one parameter of the non-resonant field while keeping the capture field constant.

In all implementations, the peak-to-peak amplitude of the non-resonant field is maintained high enough to excite the ions (via non-resonant excitation) before the ions enter a resonant excited state. For example, when the non-resonant field frequency is swept, the peak-to-peak amplitude of the non-resonant field is sufficiently high before the oscillating motion of any of the series of ions becomes resonant excitation in the changing coupling field. Is maintained, thereby ejecting each of the series of trapped ions from the binding field via non-resonant excitation.

In contrast, in the conventional resonance excitation method, the rate of change of the coupling field is controlled, and the peak-to-peak amplitude of the (fixed or changing) supplementary field (the frequency of which coincides with the frequency of the trapped ion) is also controlled. Then, it is maintained at a value that matches the frequency of movement of the ions of interest to the frequency of the applied supplementary AC field, whereby a resonance state is established for excitation. If these parameters are not properly controlled, simultaneous ejection of ions with different (but similar) m / z ratios (ie, resonance excitation of ions with first m / z ratio and slightly Second with different second m / z ratio
(Via simultaneous non-resonant excitation of ions). In typical conventional resonant excitation, the peak-to-peak amplitude of the fill field may be controlled to less than 1 volt (this avoids the interference effects described above),
In a corresponding embodiment of the present invention (using the same capture field), the supplemental signal that produces the non-resonant field can have a peak-to-peak amplitude much greater than 1 volt (this allows mass spectrometry to be more conventional). Much faster than with resonance excitation).

In a preferred embodiment of the present invention, the changing binding field continuously removes selected trapped ions from the binding field for detection (or for purposes other than detection). In another example, the present invention excites the captured ions continuously without ejecting the captured ions from the binding field.

In a preferred embodiment, the coupling field is established in a trapping region surrounded by two end electrodes and a ring electrode of a three-dimensional quadrupole ion trap. In these embodiments, the coupling field may be a quadrupole capture field created by applying a fundamental voltage to one or more ring and end electrodes, and applying a supplemental AC voltage to the end electrodes. And a replenishment station generated by RF of fundamental voltage (or D
C) The amplitude of the component (or the frequency of the RF component) can be scanned or otherwise varied during the application of the supplemental AC voltage to the end electrodes, or the supplementation while keeping the quadrupole capture field constant The parameters of the AC voltage are scanned or otherwise varied, thereby allowing for detection (or any of a variety of other purposes, including induction of ionic reactions or separations in the presence of buffer gas). 2.) Exciting ions having a range of m / z ratio continuously and non-resonantly.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a simplified schematic diagram of an apparatus useful for implementing a type of preferred embodiment of the present invention.

FIG. 2 is a stability diagram for a quadrupole capture field that can be generated by the apparatus of FIG.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS One type of preferred embodiment will be described with reference to the stability diagram shown in FIG. In those embodiments, the capture field (the capture field component of the coupling field) has a sinusoidal RF voltage component (of amplitude V and frequency Ω) and optionally a DC voltage component (of amplitude U) and is shown in FIG. Applied to the ring and end electrodes of the quadrupole ion trap of the type shown.

For the quadrupole ion trap, the well-known Matthew (Ma
The solution of the (thieu) equation specifies a stability diagram having the shape shown in FIG. Referring to FIG. 2, the parameters “a” and “q” are within the stability envelope (βr = 0, βz = 1, βr
Ions (in the area bounded by the four curves labeled = 1 and βz = 0) can be stably captured in the quadrupole capture field (parameter “e” in FIG. 2).
And "m" indicate the number of charges and the mass, respectively). The radial motion is characterized by a parameter βr that falls within the range 0 <βr <1, and furthermore, the axial motion is characterized by the range 0 <
The ions characterized by the parameter βz within βz <1 are stably trapped.

The quadrupole ion trap device shown in FIG. 1 is useful for implementing a type of preferred embodiment of the present invention. 1 includes a ring electrode 11 and end electrodes 12,13. When the switch of the basic voltage generator 14 is turned on (in response to a control signal from the control circuit 31) and the basic voltage is applied between the electrode 11 and the electrodes 12 and 13, the three-dimensional quadrupole capture A field is established in the area 16 surrounded by the electrodes 11-13. The basic voltage is composed of a sine wave voltage having an amplitude V and a frequency ω, and has a DC component having an amplitude U selectively. ω is typically in the radio frequency (RF) range.

The ion accumulation region 16 has a radius r ₀ and a vertical dimension z ₀ .
The electrodes 11, 12 and 13 are in a common mode grounded via a coupling transformer 32.

The switch of the replenishment AC voltage generator 35 is turned on (in response to a control signal from the control circuit 31), and the desired replenishment is performed.
An AC voltage is applied to the end electrodes 12 and 13 as shown (or
Alternatively, it can be applied (between the electrode 11 and one or both of the electrodes 12 and 13). In the preferred embodiment, the supplemental AC voltage signal generated by generator 35 is selected to have a peak-to-peak amplitude _Vsupp and a "non-resonant" frequency _ωsupp (described below). Changing the combined field consisting of the quadrupole capture field and the supplementary ("non-resonant") field established by the supplemental AC voltage to continuously obtain the desired capture in accordance with the present invention for detection (or for other purposes) Ions can be excited. In some embodiments, the coupling field scans or scans one or more parameters (V, ω, U, V _supp and ω _supp ) of the coupling field caused by the voltage signals output from both elements 14 and 35. This can be changed by performing a sweep (hereinafter, referred to as “scan”), whereby the desired trapped ions can be continuously excited.

When the filament 17 is powered by the filament power supply 18, the filament 17
It is directed to region 16 via 12 holes. The electron beam is in area 16
The sample molecules within are ionized so that the resulting ions can be captured in region 16 by the quadrupole capture field. The cylindrical gate electrode and lens 19 are controlled by a filament lens control circuit 21 to gate-control the electron beam and turn off and on as desired.

In one embodiment, the end electrode 13 has a through hole 23 through which ions can be ejected from the region 16 and detected by an externally placed electron multiplier detector 24. Electrometer 27 receives the current signal appearing at the output of detector 24 and converts it to a voltage signal, which is summed and stored in circuit 28 and processed in processor 29.

In the variant of the device of FIG. 1, the through-hole 23 is omitted and an in-trap detector is used instead. Such an in-trap detector can consist of the end electrode of the trap itself. For example, one or the other end electrode can be composed (or partially composed) of a phosphorescent material, which outputs photons in response to the incidence of ions on one of its surfaces. In another type of embodiment,
The in-trap detector is separate from the end electrodes, but is integrally attached to one or both of them (to detect ions, which strike the end electrodes, It does not cause significant distortion in the shape of the surface of the end electrode facing the surface). One example of this type of trap is a Faraday effect detector, in which electrically insulated conductive pins are positioned so that their tips are flush with the end electrode surface ( Desirably, the position is along the z-axis at the center of the end electrode 13). As another example, other types of ion detectors can be employed, for example, ion detectors that do not require that the ions to be detected collide directly with the detector (examples of this latter type of detector). Are referred to herein as "in-situ detectors, which include resonance output absorption detection means and image current detection means.)

The output of each in-trap detector is provided to processor 29 via the appropriate detector circuit electrodes.

In some embodiments, the generator 35 is replaced by a generator that provides a supplemental AC signal of sufficient power to the ring electrodes (rather than the end electrodes), thereby reducing the z
The ions are guided to exit the trap in the radial direction (ie, in the radial direction toward the ring electrode 11) instead of the axial direction. Applying a high-power replenishment signal to the trap so that unnecessary ions are radially ejected from the trap before detecting other ions using a detector provided along the z-axis, Since the saturation of the detector can be avoided in the meantime, the operating life of the ion detector can be sufficiently increased.

If the quadrupole capture field has a DC component, it may have both high and low frequency cutoffs and will not be able to capture ions with oscillation frequencies below the low frequency cutoff or above the high frequency cutoff.

The control circuit 31 generates a control signal and outputs the basic voltage generator 1
4, Filament control circuit 21 and supplementary AC voltage generator 35
Control. Circuit 31 sends control signals to circuits 14, 21 and 35 in response to commands received from processor 29, and sends data to processor 29 in response to requests from processor 29.

Control circuit 31 preferably comprises a digital or analog processor of the type that quickly creates and controls the frequency-amplitude band of each supplemental voltage signal represented by supplementary AC voltage generator 35 (or an appropriate digital processor). A signal processor or analog processor can be incorporated in the generator 35). Digital processors suitable for this purpose can be selected from commercially available models. With a digital signal processor, a succession of supplemental voltage signals having different frequency-amplitude bands can be quickly generated (eg, application of a notch filtered broadband signal during ion storage).

According to the invention of the present application, the trapping field is a trap region (for example,
Established in region 16) of FIG. 1, ions are formed or directed to the trapping field where they are stably trapped. The capture field is within a selected range corresponding to the capture range of the ion frequency.
Ions with an m / z ratio can be stored. A binding field (comprising a capture field and a replenishment field) is established in the trapping region and at least one parameter of the binding field is varied to continuously excite selected ones of the captured ions (eg, detection). for). The replenishment field varies periodically, and its frequency is an "non-resonant" frequency that approximately matches (but differs) the frequency of motion of the ions stably captured by the capture field alone. The replacement field may be referred to herein as a "non-resonant"("off-resonant") field.

With continuous ion excitation according to the present invention ("non-resonant" scanning or excitation), an array of trapped ions can be instantaneously ejected from the trapping region (or each ion in such an array can be targeted for a desired purpose). Can be excited to a sufficient degree for the moment) because the non-resonant field causes an increase in the trajectory of each ion in the train, and
This is because the nonresonant field can increase the trajectory of each ion to a desired magnitude within a desired short time period with a sufficient peak-peak amplitude.

In one type of embodiment, the trapped ions are continuously excited by keeping the non-resonant field constant while changing at least one parameter of the trap field component of the binding field. In another embodiment, the trapped ions are excited continuously by changing at least one parameter of the non-resonant field while keeping the trapped field constant.

In all embodiments, the peak-to-peak amplitude of the non-resonant field is kept high enough to excite the ions (via a non-resonant excitation mechanism) before the ions become resonantly excited. For example, as the non-resonant field frequency is swept, the peak-to-peak amplitude of the non-resonant field is held high enough to eject each successive trapped ion from the coupled field via non-resonant excitation, which is Permanent motion of all ions within is performed before it becomes resonant excitation in the changing coupling field.

In contrast, in conventional resonant excitation methods, the rate of change of the coupling field parameters and the peak-to-peak amplitude of the (constant or changing) supplementary field, whose frequency coincides with the permanent frequency of the trapped ions, is controlled. , Simultaneous ejection of ions with different (but similar) m / z ratios (ie,
(i.e., via a simultaneous non-resonant excitation of an ion having an m / z ratio and a second ion having a second m / z ratio slightly different from the first m / z ratio). You.
In typical conventional resonance excitation, the peak-to-peak amplitude of the fill field must be controlled to less than 1 volt (to eliminate the interference effects described above), but the corresponding embodiment of the present invention (identical to In those that employ a capture field, the supplementary signal that produces the non-resonant field can have a peak-to-peak amplitude much greater than 1 volt (the mass spectrometry performs much faster than with conventional resonant excitation). Is possible).

Referring to FIG. 2, the non-resonant field component of the changing coupling field according to the present invention excites successive trapped ions in the following manner. The frequency of motion of each trapped ion is defined by a parameter located at a point within the stable envelope (in embodiments where the trapped field is not a quadrupole field, the shape of the stable envelope will differ from that of FIG. 2). be able to).
The non-resonant field component of the changing coupling field excites each ion in the continuum and expands the trajectory of the ion without destabilizing the ion (via non-resonant excitation). In other words, during non-resonant excitation, the parameters of ion motion continue to be located at some point within the stability envelope. Each ion changes before the point where the ion is located within the stability envelope coincides with the resonance point (ie, before the frequency of the ion motion matches the frequency of the applied supplemental AC signal). It is excited to a desired extent (via non-resonant excitation) within a desired time (before resonance excitation in the binding field).

In a preferred embodiment, the changing binding field continuously ejects selected trapped ions from the binding field for detection (or for non-detection purposes). In another embodiment, the present invention excites the captured ions continuously without ejecting them from the binding field.

In a preferred embodiment, the coupling field is established in a trapping region (eg, region 16 shown in FIG. 1) of a three-dimensional quadrupole ion trap (eg, shown in FIG. 1). In those embodiments, the coupling field comprises a quadrupole capture field created by applying the above-described fundamental voltage to one or more ring and end electrodes of the trap, and a supplemental AC voltage to the end. And a non-resonant fill field created by application to the electrodes. The amplitude of the RF (or DC) component of the fundamental voltage (or the frequency of the RF component) can be scanned or otherwise altered while the supplemental AC voltage is applied to the end electrodes, or the quadrupole capture field Can be held constant while scanning or otherwise changing the parameters of the refill AC voltage, thereby detecting ions with a range of m / z ratios (or the presence of buffer gas). It can be excited continuously (for any of a variety of other purposes, including inducing ionic reactions or separations within).

A second supplemental field is superimposed on the capture field (before or during the non-resonant field is superimposed on the capture field) and unwanted ions having m / z ratios within a second selected range are removed from the binding field. Where the second replenishment field comprises frequency components in the low frequency range from the first frequency to the notch frequency band and frequency components in the high frequency range from the notch frequency band to the second frequency. And the frequency range spanning the first frequency and the second frequency includes the acquisition range. Such a second replenishment field ejects ions from the trapping area (different from the selected ions), thereby accumulating unwanted ions that would otherwise prevent a continuous mass spectrometry operation. Hinder.

In a variation of the above-described embodiment, the second fill field has two or more notch bands (ie, no frequency components). For example, the second supplementary field includes a frequency component in a low frequency range between the first frequency and the first notch frequency band and a frequency component in an intermediate frequency range between the first notch frequency band and the second notch frequency band. And a frequency component in a high frequency range from the second notch frequency band to the second frequency. For many mass spectrometry applications, each of the second supplemental field frequency components is desirably 10
Has an amplitude ranging from mV to 10 volts.

In some embodiments, one or more parameters of the binding field may be varied to perform the (MS) ⁿ mass spectrometry operation (where n = 2, 3, 4, or more) to capture trapped ions. Are continuously excited. In such (MS) ⁿ operations, the binding field is changed (eg, by switching the non-resonant field components of the binding field and changing its frequency), causing the separation of parent or daughter ions, Performed in a different manner (eg, by being swept or scanned) to perform mass analysis of daughter ions.

In any of the embodiments described above, the capture and non-resonant fields are established by applying a voltage signal to the ion trap device electrode surrounding the trapping region. In a preferred embodiment, the capture field is a quadrupole field determined by a sinusoidal fundamental voltage, which is applied to one or more of the ring and end electrodes of the quadrupole ion trap. It has a DC voltage component (of amplitude U) and an RF voltage component (of amplitude V and frequency ω).

In a preferred embodiment, a buffer or collision gas (such as, but not limited to, helium, hydrogen, argon, or nitrogen) is provided during any part of the experimental and / or mass spectrometry steps. Directed to or removed from the trap region (ie, during the step of changing the coupling field) to improve mass resolution and / or sensitivity.

In another embodiment of the present invention, the capture field component of the coupling field is a hexapole (or octupole or higher order multipole) capture field, which generates a sinusoidal (or other periodic) fundamental voltage. It is established by applying to the electrodes of a hexapole (or octupole or higher order multipole) ion trap.

In any of the embodiments of the present invention, while changing the binding field, the rate of change of one or more parameters of the binding field is controlled to achieve the desired mass spectrometry, while changing the binding field. Automatic sensitivity control methods can be used, and discontinuous mass spectrometry can be performed while changing the binding field (eg, the binding field can be changed by superimposing a continuous non-resonant field on it, In that case, each non-resonant field has a frequency selected to excite ions of an arbitrarily selected m / z ratio), the coupling field may include a second supplementary field, which may include, for example, a mass A frequency selected to eliminate leakage of permeable gas into the sealed ion trap (eg, sealed by an O-ring) and any other unwanted m / z ratio interference associated with the analytical operation Band 1 or 2 in
Can have a frequency band that includes more than one notch (ie, no frequency is present), and the coupling field can include one or more “pump” fields (each having substantially the same space as the capture field). With shape). The fields are selected, for example, so that the combined capture and pump fields are appropriately selected to perform the desired mass spectrometry operation, such as a chemical ionization (CI) operation or a selective reactive ion CI operation. A frequency band that includes one or more notches in the defined frequency band, during which the ion detector can be protected from damage due to the presence of unwanted ions, and in the presence of a coupling field, guided to the ion trap. The energy of the generated electrons can be controlled so that they do not create unwanted ions (eg, by bombardment in a trap and / or associated vacuum chamber, by ionizing CI and / or solvent gas). A binding field can be established in the ion cyclotron resonance (ICR) trap, and the binding field can be altered to detect ions in the ICR trap. Different gas pressures can be maintained in the ion implantation and transfer system, the ion trap and / or the ion detector to optimize the performance of the entire analysis, an ion trap or a vacuum system can be used, It has an O-ring or permeable membrane designed to supply airborne gas to the region of the binding field, and one or more gases are ionized and stored for use in performing CI or charge exchange reactions, or Gases that are not ionized can collide or cool the trapped ions, accumulate and / or concentrate the analyzed ions, and in ion trap mass spectrometers with electrode structures that function as a vacuum chamber in the mass spectrometer. The coupling field is designed to have a frequency-amplitude band to remove unnecessary ions from the electrode structure. That.

Various other modifications and variations of the above-described method of the present invention will be apparent to those skilled in the art without departing from the scope and spirit of the present invention. Although the invention has been described with reference to certain preferred embodiments, it should be understood that the invention is not to be unduly limited to such specific embodiments, as set forth in the following claims. .

Claims (22)

(57) [Claims] 1. A quadrupole ion trap device comprising: (a) forming a trap region capable of stably trapping ions having a mass-to-charge ratio within a selected range; and (b) applying a voltage to said quadrupole ion. Exciting the selected trapped ions in the trapping region by applying to at least one electrode of a trapping device, wherein the step (b) comprises changing the parameter of the voltage. Holding the peak-to-peak amplitude in the trapping region substantially high, so that before the selected trapped ions become resonantly excited,
A method comprising continuously exciting the selected trapped ions by non-resonant excitation. 2. The method of claim 1 wherein said peak-to-peak amplitude is greater than 1 volt. 3. The method of claim 1, wherein said parameter is an amplitude or a frequency of said voltage. 4. The method of claim 1 wherein said voltage is a sinusoidal fundamental voltage signal having an RF voltage component of amplitude V and frequency ω or a sine wave supplemental voltage signal of amplitude V _supp and frequency ω _supp . 5. The method of claim 4, wherein said sinusoidal fundamental voltage also has a DC voltage component. 6. The method of claim 1, wherein said step (b)
Controlling the rate of change of said parameters to achieve the desired mass spectrometry. 7. A step of: (a) forming a trap region in a quadrupole ion trap device capable of stably capturing ions having a mass-to-charge ratio within a selected range; and (b) applying a voltage to said quadrupole ion. Exciting the selected trapped ions in the trapping region by applying to at least one electrode of a trapping device, changing the parameter of the voltage to substantially increase the peak-to-peak amplitude in the trapping region. Holding, so that before the selected trapped ions become resonantly excited,
Exciting the selected trapped ions by non-resonant excitation to perform mass spectrometry discontinuously. 8. A step of forming in the quadrupole ion trap device a trap region capable of stably trapping ions having a mass-to-charge ratio within a selected range; and (b) selecting within the trap region. Exciting the captured ions, wherein the signal for the excitation has a frequency band including at least one notch in a selected frequency band, and a signal forming the ion trap region during the step. Exposing the selected trapped ions by non-resonant excitation before the selected trapped ions become resonantly excited. . 9. A step of forming a trap region capable of stably trapping ions having a mass-to-charge ratio in a selected range in a quadrupole ion trap device; and (b) selecting a trap region in the trap region. Exciting the trapped ions, during which the peak-to-peak amplitude of the signal forming the ion trapping region is maintained substantially high, such that the selected trapped ions undergo resonance excitation. Before the selected trapped ions are excited by specific resonance excitation, and within the ion trapping area, the trajectory of each of the selected trapped ions is expanded to a desired size within a desired time. Mass spectrometry method comprising the steps of: 10. A step of forming a trap region capable of stably trapping ions having a mass-to-charge ratio within a selected range in a quadrupole ion trap device; and (b) selecting a trap region in the trap region. Exciting the trapped ions to keep the peak-to-peak amplitude of the signal forming the ion trap region substantially high, so that the selected trapped ions are not excited before resonance excitation. (C) guiding at least one of a collision gas or a buffer gas to the trap region to improve at least one of mass resolution and sensitivity. Method. 11. A step of forming two trap regions overlapping with an ion trap region of a quadrupole ion trap device in order to stably capture ions having a mass-to-charge ratio within a selected range. (B) maintaining substantially high peak-to-peak amplitudes of signals for forming the two trapping regions in the ion trapping region to continuously excite selected trapped ions; Scanning at least one parameter, wherein said step (b) fixes one of said two trapping regions while keeping the peak-to-peak amplitude in the other trapping region substantially high, whereby the said A mass spectrometry method comprising the step of continuously exciting the selected trapped ions by non-resonant excitation before the selected trapped ions become resonantly excited. . 12. The method of claim 11, wherein said ion trapping region is formed by applying a basic voltage to at least one electrode of a quadrupole ion trap device.
Further, the method (b) includes a step of scanning the amplitude of the component of the basic voltage. 13. The method of claim 11, wherein said ion trapping region is formed by applying a fundamental voltage to at least one electrode of a quadrupole ion trap device.
Further, the step (b) includes a step of scanning a frequency of the basic voltage. 14. A quadrupole ion trap device comprising: (a) forming a trap region capable of stably capturing ions having a mass-to-charge ratio within a selected range; and (b) selecting a trap region in the trap region. Maintaining the peak-to-peak amplitude of the signal forming the trapping region substantially high to continuously excite the trapped ions captured, and scanning at least one parameter of the signal for forming the trapping region; Wherein the step (b) is a step of scanning a parameter of the signal forming the trap region by one parameter, and keeping a peak-to-peak amplitude of the signal forming the trap region substantially high; Thereby, before the selected trapped ions are excited by resonance, the step of continuously exciting the selected trapped ions by the non-resonant excitation action is performed. Mass spectrometry method comprising. 15. The method of claim 14, wherein said ion trapping region is formed by applying said supplemental AC voltage to at least one electrode of a quadrupole ion trap device, and said step (b) further comprises: Scanning the amplitude of a component of the supplemental AC voltage. 16. The method of claim 14, wherein said ion trapping region is formed by applying a replenishing AC voltage to at least one electrode of a quadrupole ion trap device, and said step (b) further comprises the step of: A method comprising scanning the frequency of an AC voltage. 17. A quadrupole ion trap device comprising: (a) forming a trap region capable of stably capturing ions having a mass-to-charge ratio within a selected range; and (b) selecting a trap region in the trap region. Scanning at least one parameter of a signal for forming the ion trap to continuously excite the captured ions, wherein the signal for excitation comprises at least one notch in a selected frequency band. And keeping the peak-to-peak amplitude of the signal forming the ion trap region substantially high during the process, so that the selected trapped ions become resonantly excited. And continuously exciting the selected trapped ions by a non-resonant excitation action. 18. A quadrupole ion trap device comprising: (a) forming a trap region capable of stably trapping ions having a mass-to-charge ratio within a selected range; and (b) selecting within the trap region. Scanning at least one parameter of a signal for forming the ion trap to continuously excite the trapped ions, wherein during step (b) the signal has a sufficiently large peak. Having a peak amplitude, whereby the selected trapped ions are excited by non-resonant excitation before the selected trapped ions become resonantly excited, and the trajectory of each of the selected trapped ions is changed. Magnifying to a desired size within a desired time. 19. A quadrupole ion trap device comprising: (a) forming a trap region capable of stably trapping ions having a mass-to-charge ratio within a selected range; and (b) selecting within the trap region. Scanning at least one parameter of the signal to form the ion trapping region to continuously excite the trapped ions captured to keep the peak-to-peak amplitude substantially high;
(C) continuously exciting the selected trapped ions by non-resonant excitation before the selected trapped ions become resonantly excited; and (c) placing at least one of a collision gas and a buffer gas in the trap region. And improving at least one of mass resolution and sensitivity. 20. The method of claim 1, wherein said step (b) comprises continuously exciting said selected trapped ions for detection. 21. The method of claim 1, wherein step (b) comprises continuously exciting the selected trapped ions for ejection from the trapping region. 22. The method of claim 1, wherein said step (b) is continuously excited to eject said selected ions from said trapping region, and is subsequently located outside said trapping region. Detecting by the detector.